Adverse reactions experienced by patients receiving triacetyl-6- azauridine (azaribine) for severe recalcitrant psoriasis. a. Central Nervous System Toxicity: We have completed several studies designed to determine the cause of central nervous system toxicity. Hyperacidity of the stomach could cleave the acetyl groups producing the less absorbable AzUR with subsequent metabolism to AzU. The CSF of neurotoxic patients does not contain TA-AzUR and the offending metabolite appears to be AzU. This metabolite has been found at significant levels, up to 103 nanomoles per ml, in neurotoxic patients taking TA-AzUR while non-neurotoxic controls have less than 2 nanomoles per ml of AzU. The source of the AzU in the CSF appears to be the result of metabolism of AzUR in the lower gastrointestinal tract. At the pH normally found in the stomach, a significant portion of the TA-AzUR might be converted to AzUR which is less absorbable and could reach the lower gastrointestinal tract where it would be presumably broken down to AzU, be absorbed, and produce CNS toxicity. We are also investigating the serum binding properties of TA-AzUR, AzUR, and AzU. Our previous studies have shown that TA-AzUR is approximately 50 percent bound to serum proteins, AzUR is approximately 1 percent bound, while AzU is about 9 percent bound at 0.1 mM/ml concentrations. b. Thromboembolic Phenomena: There appears to be an increased incidence of thromboembolic episodes in patients receiving azaribine for psoriasis. We then initiated retrospective studies to test the hypothesis that thromboembolic episodes occurred more frequently in patients with psoriasis, & similar retrospective studies at the University of California at San Francisco and Wadsworth V.A. Hospital, Los Angeles, have corrobarated our findings. In prospective studies of psoriasis and occlusive vascular disease, we plan to examine the cutaneous vasculature of psoriatic patients before and after various treatment modalities, since changes in structure may offer clues to the causes of vascular diseases in psoriasis. c. Cyclic-AMP in Psoriasis: Studies on the use of topical cyclic nucleotides in psoriasis were unproductive. Altered Immune Response in Cutaneous Disease (Psoriasis and Vitiligo). (Text Truncated - Exceeds Capacity)